Issue Forty-Five July standards of CLINICAL CASE MANAGEMENT NEWSLETTER. The Calgary Animal Referral & Emergency Centre Animal Hospital

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1 standards of CLINICAL CASE MANAGEMENT NEWSLETTER 1 The Calgary Animal Referral & Emergency Centre Animal Hospital

2 Diagnosis and Management of Recurrent Urinary Tract Infections Lisa Shearer, BSc, DVM, DVSc, Diplomate ACVIM (SAIM) Urinary tract infections (UTIs) are most commonly a result of ascending bacterial colonization from the urogenital tract The urinary tract possesses a variety of host defenses intending to prevent UTIs Normal micturition (adequate urine flow, appropriate volume and frequency of voiding) allows for flushing of bacterial organisms from the lower urinary tract (LUT) prior to establishment of infection Urine itself possesses various antimicrobial properties including extremes in urine ph, high osmolality and a high concentration of urea to help prevent UTIs Additionally, antimicrobial intrinsic properties of the urothelium (eg surface glycosaminoglycans, cellular exfoliation, etc) and mechanical/anatomical factors of the LUT (eg urethral high pressure zone, peristalsis, prostatic antibacterial fraction, length of urethra, etc) are important in prevention of ascending urinary infections Recurrent urinary tract infections are a common urological problem and reason for referral in small animal veterinary patients Development of UTIs is most common in spayed females, following by neutered males, then intact females and lastly intact males In cats, UTIs are more common in cats greater than 10 years of age than in young cats When evaluating patients for recurrent urinary tract infections, it is first important to distinguish the two types of infection recurrence: relapse versus reinfection Relapse implies incomplete resolution/persistence of the infection with the same species and serologic strain of microorganism occurring usually within several weeks of discontinuation of antimicrobial therapy Relapse of UTIs arises for several reasons including: Inappropriate antibiotic selection, dose, treatment duration Owner compliance should be evaluated Failure to eradicate underlying causes such as uroliths, neoplasia, etc Presence of a nidus of infection inaccessible to the antibiotic such as pyelonephritis, prostatitis, neoplasia, other Lower urinary tract anatomical or functional defects that lowers resistance to bacterial colonization Conversely, re-infection implies the recurrence of infection with microorganisms of a different strain from the original UTI Re-infection can arise in several situations: Underlying systemic illness such as diabetes mellitus (glucosuria, formation of a dilute urine), hyperadrenocorticism (alteration in immune competence, alteration of urine composition/dilute urine), other Failure to remove predisposing factors such as abnormal perivulvar conformation, perivulvar dermatitis, incomplete voiding/urine stasis, disruption/damage of urothelium (urolithiasis, neoplasia), other Multi-organism infections with only successful treatment of sensitive organisms Iatrogenic causes such as perineal urethrostomies in cats, other 2 wwwcarecentrecom facebookcom/carecentre

3 Differentiation of relapse versus re-infection is straightforward when the bacterial strain isolated at the time of infection recurrence is different from the initial isolate (eg Staph spp and E coli); however, distinguishing between two isolates of Ecoli can be more challenging Diagnostic Approach Typically, diagnostic evaluation for dogs with recurrent UTIs should include the following diagnostic testing with the goal to identify underlying contributing factors as outlined above: Careful review of history including evaluation of owner compliance with previous antimicrobial therapy, other clinical symptoms suggestive of other systemic conditions and questioning regarding other concurrent therapy that may be contributing to infection recurrence (eg corticosteroid therapy, etc) Physical examination with a thorough evaluation of the lower urinary tract (eg vulvar conformation, perivulvar skin appearance, etc) and a rectal examination for evaluation of the urethra (for masses or uroliths) and prostate assessment Complete blood count Serum biochemical profile Urinalysis Urine culture Abdominal radiographs Abdominal ultrasound Other ancillary diagnostic testing that could be performed should other historical, physical or biochemical data be suggestive would include: Testing for hyperadrenocorticism (ACTH stimulation test or low dose dexamethasone suppression test) Retrograde contract radiography (to evaluate urethra, etc) Cystoscopy (recommended if the above diagnostic evaluation has not identified an underlying predisposing factor/disease) o Helps to exclude contributing factors such as neoplasia, polyps, anatomical abnormalities, or urotliths o Also provides the opportunity for mucosal biopsy for culture, cytology and histopathology Culture of urethral/bladder tissue or uroliths may be more sensitive than routine urine culture for detection of UTIs (eg tissue/urolith cultures may be positive despite a negative routine urine culture) Therapeutic Approach to Recurrent Urinary Tract Infections Treatment of recurrent UTIs should first be directed at eradication of any underlying causes as outlined above (eg episioplasty, cystotomy for removal of cystoliths, treatment of diabetes mellitus, etc) Antimicrobial therapy for UTIs should be selected based on culture and sensitivity assessment of a urine sample collected in a sterile manner by cystocentesis This provides information about in vitro sensitivity and therefore, ideally, a repeat urine culture is performed approximately 7 days into antimicrobial therapy to ensure adequate in vivo efficacy of the selected treatment In patients with recurrent infections, provided the culture performed 7 days into treatment revealed no bacterial growth, then treatment 3 wwwcarecentrecom facebookcom/carecentre

4 should be continued at an appropriate dosage for a total of 3-6 weeks A more protracted antibiotic course (eg 6-8 weeks) may be required in cases with suspected prostatic or kidney involvement To evaluate and monitor response to therapy, a repeat urinalysis and urine culture is recommended 1 week and again 1 month after discontinuation of antimicrobial therapy As previously mentioned, antimicrobial selection for UTIs should be based upon urine culture and sensitivity results Another factor to consider, is that it should be assumed that male dogs with UTIs have prostatic involvement As such, in male dogs with UTIs, antibiotic selection should also provide good prostatic penetration such as fluoroquinolones, clindamycin, trimethoprim-sulfa, chloramphenicol and erythromycin Bactericidal antibiotics antibiotics such as fluoroquinolones would be preferred for treatment of chronic prostatitis Antibiotics which achieve poor prostatic penetration include ampicillin/amoxicillin, cephalosporins and aminoglycosides and these antibiotics should therefore be avoided in cases of bacterial prostatitis Preventative Therapy For Repeated Reinfection Repeated re-infection (> 2-3 UTIs in 6 month period) justifies preventative therapy only after a thorough diagnostic evaluation has not identified an underlying cause or in some cases when the precipitating factor cannot be removed Prophylactic therapy involves single dose administration of an antibiotic once before a 6-12 hour period when urine will be retained in the bladder (eg in the evening prior to bed time after the patient has urinated such that the antibiotic will remain concentrated in the urine overnight) The goal of prophylactic therapy is in attempting to prevent re-establishment of infection and therefore therapy must be in place in a sterile urine prior to re-infection to be effective Antibiotic selection is based on susceptibility of the most recent bacterial isolate with a dose ½ to 1/3 of the usual total daily dose Therapy is continued for approximately 6 months and ideally urine is cultured every 4 weeks If sterile urine is documented for 6 months, then prophylactic therapy can be discontinued and the patient is monitored for re-infection This approach can only be instituted once appropriate therapy for the UTI has been instituted and the infection has been resolved It should be noted that this approach is also not effective for relapses of infection due to a nidus within the urinary tract Pulse therapy (eg antimicrobial therapy for 3-5 days every few weeks) is neither recommended nor effective for management of recurrent UTIs and is only likely to induce multiple drug resistance complicating long-term therapy of recurrent infections An alternative to prophylactic antimicrobial therapy is management with methenamine Methenamine is a urinary tract antiseptic which is effective when urine is maintained at a ph <60 Methenamine is converted to formaldehyde in an acidic urine ph and bacteria can not acquire resistance to formaldehyde and therefore may be effective in patients with re-infections As with prophylactic antimicrobial therapy, the urine must be sterile prior to commencement of therapy This product should not be used in patients with metabolic acidosis (eg chronic renal failure) as methenamine can cause systemic acidosis It should be noted that cats do not tolerate this product as well as dogs and it is not effective with UTIs secondary to urease-producing microbes as these will lead to an alkaline urine ph 4 wwwcarecentrecom facebookcom/carecentre

5 Products containing methylene blue should be avoided (particularly in cats) The dose of methenamine is not well established but recommended doses are mg/kg PO q 8-12 hours In some cases, urinary acidifiers or an acidifying diet may be required Lisa Shearer, BSc, DVM, DVSc, Diplomate ACVIM (SAIM) Dr Shearer is a member of the CARE Centre Internal Medicine team References: Adams LG, Syme HM Canine lower urinary tract diseases, in Textbook of Veterinary Internal Medicine, ed Ettinger SJ and Feldman BF, WB Saunders, Philadelphia, 2004 Gatoria IS Comparison of three techniques for the diagnosis of urinary tract infections in dogs with urolithiasis J Small Anim Pract 2006;47: Hamaide AJ, Martinez SA, Hauptman J, et al Prospective comparison of four sampling methods (cystocentesis, bladder mucosal swab, bladder mucosal biopsy, and urolith culture) to identify urinary tract infections in dogs with urolithiasis J Am Anim Hosp Assoc 1998;34: Lightner BA, McLoughlin MA, Chew DJ, et al Episioplasty for the treatment of perivulvar dermatitis or recurrent urinary tract infections in dogs with excessive perivulvar skin folds: 31 cases ( ) J Am Vet Med Assoc 2001;219: Seguin MA, Vaden SL, Altier C, et al Persistent urinary tract infections and reinfections in 100 dogs ( ) J Vet Intern Med 2003;17: Senior DF Management of urinary tract infections, in BSAVA Manual of Canine and Feline Nephrology and Urology, ed Elliot J and Grauer GF, BSAVA, Gloucester, wwwcarecentrecom facebookcom/carecentre